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Remote Memory

To further identify the internal structures underlying the real-time memory encoding, we have employed the agglomerative hierarchical clustering and sequential MDA Fig. 1. Large-scale simultaneous monitoring of 260 CA1 cells in mice during various mnemonic startling episodes. (A) A set of new behavioral paradigms that involve categorical variables is used to create discrete episodic memories for mice a sudden blow of air to the animal's back (in mimicking an owl attack from sky) a short...

In the so-called standard model of memory consolidation (Fig. 2), the hippocampus is believed to rapidly integrate and bind together information transmitted from distributed cortical networks that support the various features of a whole experience in order to form a coherent memory trace. Consolidation of this new memory trace at the cortical level would then occur slowly via repeated reactivation of hippocampal-cortical networksr to progressively increase the strength and stability of...

In Drosophila, MBs seem especially involved in olfactory learning and memory and not in visual learning (Wolf et al. 1998). Flies can remember that a visual pattern represents a danger because this cue has been associated with heat (for review, see Heisenberg et al. 2001). Recently, using a variety of neurogenetic tools, Liu et al. (2006) identified a central brain structure, the fan-shaped body (FB), as being involved in visual memory (Fig. 4). After showing that the adenylate-cyclase Rut was...

Habit memory is a form of nondeclarative memory that involves slowly acquired associations between stimuli and responses. In contrast to declarative memory, nondeclar-ative memory operates outside of awareness and is expressed through performance rather than conscious recollection. Declarative memory depends on the integrity of the medial temporal lobe. By contrast, habit memory is thought to be supported by the basal ganglia (Mishkin and Petri 1984). It has been difficult to study habit...

Studies with transgenic animals have strongly suggested that ADDLs might be responsible for synapse elimination (Mucke et al. 2000), an aspect of neuropathology that in humans affords the best correlate of dementia (Masliah et al. 1993). This possibility has been verified directly in cell biology experiments. After 24 hours of exposure to ADDLs, the spiny post-synaptic specializations manifest a significant decrease in density, with an overall loss of spines equaling 50 . Spine loss of this...

With the identification of the neural clique as a basic coding unit and the feature-encoding pyramid within the clique assemblies, we can further convert (through matrix inversion) those distinct ensemble representations observed in a low-dimensional encoding-subspace into a string of binary activation codes with 1s and 0s (Fig. 3). This binary assignment - 1 for the active state and 0 for the inactive state of neural cliques -is based on the idea that the activity state of a neural clique can...

The use of aversive learning paradigms in the study of learning and memory consolidation has been favored principally due to the utility of single session, or even single trial, learning. Similarly, investigation of memory reconsolidation has largely involved fear conditioning or avoidance memories. However, there is a growing literature on the reconsolidation of non-aversive and appetitive memories in general, the findings are consistent with those of aversive conditioning studies. Object...

Through examining the overall organization of neural clique assembly involved in startle memory encoding, it is clear that the internal CA1 representations of any given startle episode involves a combinatorial set of neural cliques, invariantly consisting of the general startle clique, sub-general startle clique, startle identity-specific clique, and context-specific startle clique (Lin et al. 2005,2006). Thus, each clique assembly is organized in a categorical hierarchy manner and invariantly...

When it comes to studying temporally graded retrograde amnesia, animal models offer a certain number of advantages over human case studies (Squire 1992). First, the content and age of memories can be rigorously assessed across time points in a prospective manner, two parameters that are difficult to control for in humans, where studies rely almost exclusively on retrospective questionnaires. Second, the location and extent of lesions are strictly circumscribed to the brain area of interest. As...

Assays based on oligomer-selective antibodies have provided compelling evidence that oligomers are bona fide components of AD pathology oligomers occur in human brain and are strikingly elevated in AD oligomers from AD brain are structurally homologous to synthetic oligomers and hAPP mouse models of AD accumulate oligomers as predicted. Oligomers found in CSF, moreover, appear to provide a significant biomarker of AD that is potentially of value for future clinical diagnostics. To assess...

Confocal immunofluorescence microscopy shows that the synaptic targeting of ADDLs frequently localizes to dendritic spines, as illustrated here by a neuron double-labeled for ADDLs and CaMKII (Fig. 2). While other sites also may be targeted, spines are particularly interesting because they contain the post-synaptic signal transduction components of excitatory synapses. Signaling events within spines orchestrate the Fig. 2. Localization of ADDL binding sites to dendritic spines. ADDLs act as...

The regular structure of the grid field and its relative independence of landmarks in the environment implicate the grid cell as part of a universal, path-integration-based spatial metric (Hafting et al. 2005 Fuhs and Touretzky 2006 McNaughton et al. 2006). A role for grid cells in path integration is also consistent with the inability of animals with entorhinal cortex lesions to calculate a return path to their home cage on the basis of self-motion cues (Parron and Save 2004). How the position...

LTP is not memory but is widely recognized as a good experimental paradigm for the study of memory mechanisms. The rapid impact of oligomers on LTP thus is intuitively appealing in its relevance to AD, and in 1998 we proposed a new hypothesis that attributed early memory loss to oligomer-induced failure in synaptic plasticity (Lambert et al. 1998). The experimental foundation for this concept has been substantiated in multiple investigations (Chen et al. 2000 Vitolo et al. 2002 Klyubin et al....

Semantic memory refers to the factual information that we acquire about the world. It has been observed that the ability to acquire new semantic memory is impaired following medial temporal lobe damage. Thus, patients with damage limited to the hippocampal region have moderate difficulty in acquiring new semantic memory, whereas patients with damage extendingbeyond the hippocampus into adjacent medial temporal lobe structures have a more severe impairment. From these observations, one could...